TOPICAL DELIVERY OF o•-TOCOPHEROL 163 The following chemicals were obtained directly from the manufacturer and used without purification: SD alcohol, Eastman (TN) isopropyl myristate (IPM) and mineral oil, Sigma Chemical Company (NJ) diisopropyl adipate (DIA), Ceraphyl © 230, isocetyl alcohol, and Ceraphyl ©, ISP Vandyk (NJ) carbomer, Carbopol ©, B F Goodrich (OH) DEA-cetyl phosphate, Roche Vitamins and Fine Chemicals (NJ) diazazodinyl urea and germall, Sutton Laboratories (NJ) ethomeen C/25, Akzonobel (IL) hydroxypropyl cel- lulose, Klucel ©, Hercules Co., Germany Tween©20, polyoxyethylene (20) sorbitan monolaurate, and Tween©80, polyoxyethylene (20) sorbitan monooleate, ICI Surfactants (DE) and Transcutol, diethylene glycol monoethyl ether, Gattefosse (France). Scintil- lation fluid Scintiverse, reagent alcohol, and glacial acetic acid were of HPLC grade and were obtained from Fisher Scientific (Springfield, NJ). Water refers to freshly deionized water. Tissue solubilizing fluid, Solvable TM, was purchased from Packard Instrument Co. (Meriden, CT). Transparent tape # 800 was purchased from 3M Packaging Systems Division (St. Paul, MN). All other materials were obtained from standard sources. TOPICAL FORMULATIONS Formulations for ot-Tpermeation study. All formulations were prepared on a weight/weight basis. The compositions of the formulations used in this study are shown in Tables I and II. Gels 1, 2, and 3 differed in their alcohol content. Gels 1 and 2 were purely alcoholic, with gel 2 containing a surfactant. Gel 3 was a hydroalcoholic gel. The oils in the case of the macroemulsion formulation (emulsion 1) were kept at a constant ratio of diiso- propyl adipate:mineral oil, 1:1, throughout the experiment. Emulsions were made by heating the oily and aqueous phases separately (55øC) and shear mixing the two phases (aqueous added to oily) to yield creamy emulsions. Simple vortexing was sufficient to give clear microemulsions. Formulations for concentration study. The concentrations chosen for the concentration de- pendency study were 0.25%, 1%, and 4% o•-T. Prototype formulations including the IPM solution, gel 3, and emulsion 1 were made at these three concentrations of o•-T. Higher or lower amounts of o•-T were compensated for by decreasing or increasing the solvent for o•-T used in the corresponding 1% formulations (IPM for solutions, SD alcohol for gels, and the oils for emulsions). Formulations with sunscreens. Sunscreen formulations containing o•-T included gel 3 and emulsions 1 and 3. Two sunscreens were studied, octyl methoxy cinnamate (OMC) and octyl salicylate (OSal), at concentrations of 7% and 5%, respectively. The formulations Table I Topical Gel Formulations Used in the Study: o•-Tocopherol Gels Ingredient Gel 1 (% w/w) Gel 2 Gel 3 tx-T 1 SD alcohol 96 Isocetyl alcohol -- PEG-15 cocamine -- Hydroxy propyl cellulose 3 Water 1 1 91 69 -- 14 5 5 3 3 -- 8

164 JOURNAL OF COSMETIC SCIENCE Table II Topical Emulsion Formulations Used in This Study Ingredient ot-T (% w/w) Emulsion 1 a ot-T 1.00 Diisopropyl adipate 5.38 Mineral oil 5.38 DEA-cetyl phosphate 2.00 Diazazodinyl urea 0.30 Carbomer 0.30 Water 85.64 Emulsion 2 b ot-T 1 Isopropyl myristate 10 Polysorbate 80 16 Sorbitol 30 Water 43 Emulsion 3 c ot-T 1 Benzyl alcohol 21.3 Diethylene glycol monoethyl ether 16.9 Tween 20 18.1 Water 42.7 a o/w macroemulsion. b,c Microemulsion containing IPM or benzyl alcohol as oily phases. remained similar to gel 3 (Table I) and emulsions 1 and 3, given in Table II, with the difference of the added sunscreen agents. The added ingredients were compensated for by a decrease in the concentration of SD alcohol in the gels and the oily phases in the microemulsions. The ratio of the two oils for emulsion 1 was still maintained the same. Oleic acid study. For the penetration enhancer study, the IPM solution, emulsion 1, and gel 3 were studied, containing in addition to the ingredients listed in Table I and II, 1% oleic acid. A gel 3 formulation containing 5% oleic acid was also included for study purposes. A control experiment with ot-T was run simultaneously with all three for- mulations without the added oleic acid. All ot-T formulations were observed for stability for a period of two weeks. Also, to ensure that ot-T was not oxidized during manufacture itself, cold formulations imme- diately upon manufacture and two weeks later were assayed for drug content by HPLC. Details of the HPLC procedure are given elsewhere (19). RECEPTOR FLUID The receptor fluid was an aqueous solution of 0.1% polyoxyethylene oleyl ether (PEG-20 oleyl ether), a nonionic surfactant with an HLB of 16. This receptor fluid, though not physiologic, maintains adequate solubility of ot-T without affecting skin barrier function (21). The receptor was pumped at a rate of 1.5 ml/h. The apparent solubility of ot-T in 0.1% PEG-20 oleyl ether at 37øC was measured to be 1.08 mg/ml, substantially in excess of the maximum concentration in the receptor solution, thereby assuring main- tenance of the sink condition at all times.